Three case reports of radiation-induced glioblastoma after complete remission of acute lymphoblastic leukemia

Kajitani, Takumi; Kanamori, Masayuki; Saito, Ryuta; Watanabe, Yuko; Suzuki, Hiroyoshi; Watanabe, Mika; Kure, Shigeo; Tominaga, Teiji

doi:10.1007/s10014-018-0316-1

Cited by 9 publications

(14 citation statements)

References 35 publications

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“…Two patients had a hypermethylated MGMT promoter; the other 6 patients had a hypomethylated MGMT promoter. These results are consistent with those of previous reports and con rm the genetic characteristics of RIG [10][11][12][13][14][15]24]. In Case 9, the difference in the IDH1/2 mutational status between the primary and secondary tumors was helpful for establishing the diagnosis of RIG.…”

Section: Discussionsupporting

confidence: 92%

Assessment of Therapeutic Outcome and Role of Reirradiation in Patients With Radiation-induced Glioma

Ohno¹,

Miyakita²,

Takahashi³

et al. 2021

Preprint

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Background: We retrospectively reviewed the clinical characteristics and treatment outcomes to clarify the optimal therapeutic strategy, especially the role of reirradiation in patients with radiation-induced glioma (RIG). Methods: We identified patients with high-grade glioma who satisfied Cahan’s criteria for RIG in our database during 2001–2021 and analyzed the outcomes.Results: We identified 11 patients with RIG. The primary diseases included germinomas (n=2), acute lymphoblastic lymphomas (n=2), medulloblastomas (n=3), diffuse astrocytoma with isocitrate dehydrogenase (IDH) 2 mutant (n=1), pilocytic astrocytoma (n=1), pituitary adenoma (n=1), and a metastatic tumor from lung cancer (n=1). The median latency period was 17 years (range: 9–30 years). The RIGs included glioblastoma with IDH 1/2 wild-type (n=7), glioblastoma not otherwise specified (n=2), anaplastic astrocytoma with IDH1/2 wild-type (n=1), and anaplastic astrocytoma not otherwise specified (n=1). All patients underwent tumor removal or biopsy, 5 patients postoperatively received reirradiation combined with chemotherapy, and 6 patients were treated with chemotherapy alone. The median progression-free and overall survival times were 11.3 and 28.3 months, respectively. The median progression-free survival time of patients treated with reirradiation and chemotherapy (n=5) tended to be longer than that of patients that received chemotherapy alone (n=6) (17.0 vs 8.1 months; p=0.45); the median survival time was similar (29.6 vs 27.4 months; p=0.28). Local recurrences were observed less frequently in patients who received reirradiation combined with chemotherapy (50%) than in those who received chemotherapy alone (100%; p=0.046). None of the patients developed radiation necrosis. In one case, the different IDH2 mutational states between the primary and secondary tumors were useful for diagnosing the secondary tumor as RIG. Conclusions: RIG can occur more than 20 years after successful treatment of the primary disease using radiotherapy; thus, follow-up times should be extended to 30 years. Reirradiation combined with chemotherapy appears to be feasible and have favorable outcomes. Identifying the IDH1/2 mutational status can have a diagnostic effect on establishing RIG in recurrent gliomas.

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Section: Discussionsupporting

confidence: 92%

Assessment of Therapeutic Outcome and Role of Reirradiation in Patients With Radiation-induced Glioma

Ohno¹,

Miyakita²,

Takahashi³

et al. 2021

Preprint

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“…Historically, RIGs have been clinically diagnosed as diffuse intrinsic pontine glioma (DIPG), 19 , 40 anaplastic astrocytoma (AA), 24 , 30 , 31 , 36–38 , 41 , 46 , 47 , 63 or GBM 22–25 , 28 , 29 , 34 , 38 , 39 , 41 , 42 , 45 , 46 , 48 , 50 based primarily on histological and/or radiographical characteristics. In very rare cases, the diagnosis of anaplastic ependymoma has also been reported.…”

Section: Discussionmentioning

confidence: 99%

Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis

Whitehouse

Howlett

Federico

et al. 2021

Neuro-Oncology Advances

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Background Cranial radiation therapy is essential in treating many pediatric cancers, especially brain tumors, however its use comes with the risk of developing second malignancies. Cranial radiation-induced gliomas (RIGs) are aggressive high-grade tumors with a dismal prognosis, for which no standard therapy exists. A definitive molecular signature for RIGs has not yet been established. We sought to address this gap by performing a systematic review and meta-analysis of the molecular features of cranial RIGs. Methods A systematic review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English language articles and case reports referring to radiation-induced high-grade gliomas located in the human brain that included molecular analyses were identified, evaluated and data extracted for collation. Results Of 1727 records identified, 31 were eligible, containing 102 unique RIGs with molecular data. The most frequent genetic alterations in RIGs included PDGFRA or TP53 mutations, PDGFRA or CDK4 amplifications, and CDKN2A deletion, along with 1q gain, 1p loss and 13q loss. Of note, mutations in ACVR1, EGFR, H3F3A, HIST1H3B, HIST1H3C, IDH2, SMARCB1 or the TERT promoter were not observed. A comparative analysis revealed that RIGs are molecularly distinct from most other astrocytomas and gliomas and instead align most closely with the pedGBM_RTK1 subgroup of pediatric glioblastoma. Conclusions This comprehensive analysis highlights the major molecular features of RIGs, demonstrates their molecular distinction from many other astrocytomas and gliomas, and reveals potential genetic drivers and therapeutic targets for this currently fatal disease.

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“… yes n.a. H3K27M(+), IDH R132H(−) 3 months Kajitani et al [ 36 ] BVS male 13 headache secondary partial QT/RT, TMZ yes GFAP(+),VIMENTIN(+),KI67(+),MGMT(−) ATRX(+), IDH−1 wt(+), H3KM27M(−), BRAFV600E(−), TP53(+) 4 months Kajitani et al [ 36 ] BVS female 16 seizures secondary partial QT/RT, TMZ yes GFAP(+), ATRX(+),VIMENTIN(+), KI67(+), MGMT(−) IDH-1 wt (+), TP53(−), BRAFV600E(−),H3K27M(−) 6 months Kajitani et al [ 36 ] BVS female 16 facial nerve paralysis secondary total QT/RT, TMZ no GFAP(+), ATRX(+), VIMENTIN(+),KI67(+) IDH-1 wt (+),BRAFV600E(−),H3K27M(−), TP53(+) alive Kumaria et al [ 37 ] BVS male 65 headache, personality disorder, dizziness primary total n.a. yes GFAP(+) IDH-1 wt(+) 17 months McClelland et al [ 38 ] …”

Section: Resultsmentioning

confidence: 99%

Glioblastoma multiforme: a multi-omics analysis of driver genes and tumour heterogeneity

et al. 2021

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Glioblastoma (GBM) is the most aggressive and common brain cancer in adults with the lowest life expectancy. The current neuro-oncology practice has incorporated genes involved in key molecular events that drive GBM tumorigenesis as biomarkers to guide diagnosis and design treatment. This study summarizes findings describing the significant heterogeneity of GBM at the transcriptional and genomic levels, emphasizing 18 driver genes with clinical relevance. A pattern was identified fitting the stem cell model for GBM ontogenesis, with an upregulation profile for MGMT and downregulation for ATRX, H3F3A, TP53 and EGFR in the mesenchymal subtype. We also detected overexpression of EGFR, NES, VIM and TP53 in the classical subtype and of MKi67 and OLIG2 genes in the proneural subtype. Furthermore, we found a combination of the four biomarkers EGFR, NES, OLIG2 and VIM with a remarkable differential expression pattern which confers them a strong potential to determine the GBM molecular subtype. A unique distribution of somatic mutations was found for the young and adult population, particularly for genes related to DNA repair and chromatin remodelling, highlighting ATRX, MGMT and IDH1. Our results also revealed that highly lesioned genes undergo differential regulation with particular biological pathways for young patients. This multi-omic analysis will help delineate future strategies related to the use of these molecular markers for clinical decision-making in the medical routine.

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Three case reports of radiation-induced glioblastoma after complete remission of acute lymphoblastic leukemia

Cited by 9 publications

References 35 publications

Assessment of Therapeutic Outcome and Role of Reirradiation in Patients With Radiation-induced Glioma

Assessment of Therapeutic Outcome and Role of Reirradiation in Patients With Radiation-induced Glioma

Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis

Glioblastoma multiforme: a multi-omics analysis of driver genes and tumour heterogeneity

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